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2. Diversity of intratumoral regulatory T cells in B-cell non-Hodgkin lymphoma

Author

Spasevska, Ivana, Sharma, Ankush, Steen, Chloé B., Josefsson, Sarah E., Blaker, Yngvild N., Kolstad, Arne, Rustad, Even H., Meyer, Saskia, Isaksen, Kathrine, Chellappa, Stalin, Kushekhar, Kushi, Beiske, Klaus, Førsund, Mette S., Spetalen, Signe, Holte, Harald, Østenstad, Bjørn, Brodtkorb, Marianne, Kimby, Eva, Olweus, Johanna, Taskén, Kjetil, Newman, Aaron M., Lorenz, Susanne, Smeland, Erlend B., Alizadeh, Ash A., Huse, Kanutte, and Myklebust, June H.

Published
2023
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4. Disruption of KLHL6 Fuels Oncogenic Antigen Receptor Signaling in B-cell Lymphoma

Author

Meriranta, Leo, primary, Sorri, Selma, additional, Huse, Kanutte, additional, Liu, Xiaonan, additional, Spasevska, Ivana, additional, Zafar, Sadia, additional, Chowdhury, Iftekhar, additional, Dufva, Olli, additional, Sahlberg, Eerika, additional, Tandaric, Luka, additional, Karjalainen-Lindsberg, Marja-Liisa, additional, Hyytiainen, Marko, additional, Varjosalo, Markku, additional, Myklebust, June H., additional, and Leppa, Sirpa, additional

Published
2024
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6. Figure S1-S8 from TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma

Author

Josefsson, Sarah E., primary, Beiske, Klaus, primary, Blaker, Yngvild N., primary, Førsund, Mette S., primary, Holte, Harald, primary, Østenstad, Bjørn, primary, Kimby, Eva, primary, Köksal, Hakan, primary, Wälchli, Sébastien, primary, Bai, Baoyan, primary, Smeland, Erlend B., primary, Levy, Ronald, primary, Kolstad, Arne, primary, Huse, Kanutte, primary, and Myklebust, June H., primary

Published
2023
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7. Supplementary Tables S1-S2 from TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma

Author

Josefsson, Sarah E., primary, Beiske, Klaus, primary, Blaker, Yngvild N., primary, Førsund, Mette S., primary, Holte, Harald, primary, Østenstad, Bjørn, primary, Kimby, Eva, primary, Köksal, Hakan, primary, Wälchli, Sébastien, primary, Bai, Baoyan, primary, Smeland, Erlend B., primary, Levy, Ronald, primary, Kolstad, Arne, primary, Huse, Kanutte, primary, and Myklebust, June H., primary

Published
2023
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8. Data from TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma

Author

Josefsson, Sarah E., primary, Beiske, Klaus, primary, Blaker, Yngvild N., primary, Førsund, Mette S., primary, Holte, Harald, primary, Østenstad, Bjørn, primary, Kimby, Eva, primary, Köksal, Hakan, primary, Wälchli, Sébastien, primary, Bai, Baoyan, primary, Smeland, Erlend B., primary, Levy, Ronald, primary, Kolstad, Arne, primary, Huse, Kanutte, primary, and Myklebust, June H., primary

Published
2023
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9. Supplementary table S1 from T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling

Author

Josefsson, Sarah E., primary, Huse, Kanutte, primary, Kolstad, Arne, primary, Beiske, Klaus, primary, Pende, Daniela, primary, Steen, Chloé B., primary, Inderberg, Else Marit, primary, Lingjærde, Ole Christian, primary, Østenstad, Bjørn, primary, Smeland, Erlend B., primary, Levy, Ronald, primary, Irish, Jonathan M., primary, and Myklebust, June H., primary

Published
2023
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10. Supplementary methods and references, Supplementary Figures 1-9 from T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling

Author

Josefsson, Sarah E., primary, Huse, Kanutte, primary, Kolstad, Arne, primary, Beiske, Klaus, primary, Pende, Daniela, primary, Steen, Chloé B., primary, Inderberg, Else Marit, primary, Lingjærde, Ole Christian, primary, Østenstad, Bjørn, primary, Smeland, Erlend B., primary, Levy, Ronald, primary, Irish, Jonathan M., primary, and Myklebust, June H., primary

Published
2023
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11. Supplementary figures 1-9 from T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling

Author

Josefsson, Sarah E., primary, Huse, Kanutte, primary, Kolstad, Arne, primary, Beiske, Klaus, primary, Pende, Daniela, primary, Steen, Chloé B., primary, Inderberg, Else Marit, primary, Lingjærde, Ole Christian, primary, Østenstad, Bjørn, primary, Smeland, Erlend B., primary, Levy, Ronald, primary, Irish, Jonathan M., primary, and Myklebust, June H., primary

Published
2023
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12. Mechanism of CD79A and CD79B support for IgM(+) B cell fitness through BCR surface expression

Author

Huse, Kanutte, Bai, Baoyan, Hilden, Vera Irene, Bollum, Lise K, Våtsveen, Thea K, Munthe, Ludvig A, Smeland, Erlend B, Irish, Jonathan Michael, Wälchli, Sébastien, and Myklebust, June H.

Subjects
Mice, B-Lymphocytes, Immunoglobulin M, Humans, Animals, Receptors, Antigen, B-Cell, Cell Count, Germinal Center, Article, CD79 Antigens
Abstract

The B-cell receptor (BCR) consists of surface-bound immunoglobulin (Ig) and a heterodimeric signaling unit comprised of CD79A and CD79B. Upon cognate antigen recognition, the receptor initiates important signals for B-cell development and function. The receptor also conveys antigen-independent survival signals termed tonic signaling. While the requirement of a CD79A/CD79B heterodimer for BCR complex assembly and surface expression is well established based on mice models, few studies have investigated this in human mature B cells. Here, we found that human tonsillar B cells with high surface expression of IgM or IgG had potentiated BCR signaling compared to BCR(low) cells, and high IgM expression in germinal center B cells was associated with reduced apoptosis. We explored the mechanism for IgM surface expression by CRISPR/Cas9-induced deletion of CD79A or CD79B in four B-lymphoma cell lines. Deletion of either CD79 protein caused loss of surface IgM in all cell lines and reduced fitness in three. From two cell lines, we generated stable CD79A or CD79B knockout clones, and demonstrated that loss of CD79A or CD79B caused a block in N-glycan maturation and accumulation of immature proteins, compatible with retention of BCR components in the endoplasmic reticulum. Rescue experiments with CD79B WT restored surface expression of CD79A and IgM with mature glycosylation, whereas a naturally-occurring CD79B G137S mutant disrupting CD79A/CD79B heterodimerization did not. Our study highlights that CD79A and CD79B are required for surface IgM expression in human B cells and illuminates the importance of IgM expression level for signaling and fitness.

Published
2022

14. Diversity of Intratumoral Regulatory T Cells in Non-Hodgkin Lymphoma

Author

Spasevska, Ivana, primary, Sharma, Ankush, additional, Steen, Chloe B., additional, Josefsson, Sarah, additional, Blaker, Yngvild Nuvin, additional, Rustad, Even H, additional, Meyer, Saskia, additional, Chellappa, Stalin, additional, Kushekhar, Kushi, additional, Kolstad, Arne, additional, Beiske, Klaus, additional, Holte, Harald, additional, Østenstad, Bjørn, additional, Kimby, Eva, additional, Olweus, Johanna, additional, Tasken, Kjetil, additional, Lorenz, Suzanne, additional, Smeland, Erlend B., additional, Alizadeh, Ash A., additional, Huse, Kanutte, additional, and Myklebust, June Helen, additional

Published
2021
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16. Heterogeneity of Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma

Author

Spasevska, Ivana, primary, Josefsson, Sarah, additional, Blaker, Yngvild Nuvin, additional, Steen, Chloe B., additional, Sharma, Ankush, additional, Kushekhar, Kushi, additional, Meyer, Saskia, additional, Kolstad, Arne, additional, Beiske, Klaus, additional, Holte, Harald, additional, Østenstad, Bjørn, additional, Kimby, Eva, additional, Olweus, Johanna, additional, Tasken, Kjetil, additional, Lorenz, Suzanne, additional, Smeland, Erlend B., additional, Alizadeh, Ash A., additional, Huse, Kanutte, additional, and Myklebust, June Helen, additional

Published
2020
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19. Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression.

Author

Rye, Inga Hansine, Huse, Kanutte, Josefsson, Sarah E., Kildal, Wanja, Danielsen, Håvard E., Schlichting, Ellen, Garred, Øystein, Riis, Margit L., OSBREAC, Lingjærde, Ole Christian, Myklebust, June H., and Russnes, Hege G.

Abstract

Sentinel lymph nodes are the first nodes draining the lymph from a breast and could reveal early changes in the host immune system upon dissemination of breast cancer cells. To investigate this, we performed single‐cell immune profiling of lymph nodes with and without metastatic cells. Whereas no significant changes were observed for B‐cell and natural killer (NK)‐cell subsets, metastatic lymph nodes had a significantly increased frequency of CD8 T cells and a skewing toward an effector/memory phenotype of CD4 and CD8 T cells, suggesting an ongoing immune response. Additionally, metastatic lymph nodes had an increased frequency of TIGIT (T‐cell immunoreceptor with Ig and ITIM domains)‐positive T cells with suppressed TCR signaling compared with non‐metastatic nodes, indicating exhaustion of effector T cells, and an increased frequency of regulatory T cells (Tregs) with an activated phenotype. T‐cell alterations correlated with the percentage of metastatic tumor cells, reflecting the presence of metastatic tumor cells driving T effector cells toward exhaustion and promoting immunosuppression by recruitment or increased differentiation toward Tregs. These results show that immune suppression occurs already in early stages of tumor progression. [ABSTRACT FROM AUTHOR]

Published
2022
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20. Abstract 1422: Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma

Author

Dillard, Pierre, primary, Köksal, Hakan, additional, Josefsson, Sarah, additional, Maggadottir, Solrun Melkorka, additional, Pollmann, Sylvie, additional, Fåne, Anne, additional, Blaker, Yngvild Nuvin, additional, Beiske, Klaus, additional, Huse, Kanutte, additional, Kolstad, Ane, additional, Holte, Harald, additional, Kvalheim, Gunnar, additional, Smeland, Erlend Bremertun, additional, Myklebust, June, additional, Inderberg, Else Marit, additional, and Wälchli, Sebastien, additional

Published
2019
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22. Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma

Author

Köksal, Hakan, primary, Dillard, Pierre, additional, Josefsson, Sarah E., additional, Maggadottir, Solrun Melkorka, additional, Pollmann, Sylvie, additional, Fåne, Anne, additional, Blaker, Yngvild Nuvin, additional, Beiske, Klaus, additional, Huse, Kanutte, additional, Kolstad, Arne, additional, Holte, Harald, additional, Kvalheim, Gunnar, additional, Smeland, Erlend B., additional, Myklebust, June H., additional, Inderberg, Else Marit, additional, and Wälchli, Sébastien, additional

Published
2019
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24. TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma

Author

Josefsson, Sarah E., primary, Beiske, Klaus, additional, Blaker, Yngvild N., additional, Førsund, Mette S., additional, Holte, Harald, additional, Østenstad, Bjørn, additional, Kimby, Eva, additional, Köksal, Hakan, additional, Wälchli, Sébastien, additional, Bai, Baoyan, additional, Smeland, Erlend B., additional, Levy, Ronald, additional, Kolstad, Arne, additional, Huse, Kanutte, additional, and Myklebust, June H., additional

Published
2019
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25. TGF-β-induced growth inhibition in B-cell lymphoma correlates with Smad1/5 signalling and constitutively active p38 MAPK

Author

Hilden Vera I, Huse Kanutte, Bakkebø Maren, Smeland Erlend B, and Oksvold Morten P

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Cytokines of the transforming growth factor β (TGF-β) superfamily exert effects on proliferation, apoptosis and differentiation in various cell types. Cancer cells frequently acquire resistance to the anti-proliferative signals of TGF-β, which can be due to mutations in proteins of the signalling cascade. We compared the TGF-β-related signalling properties in B-cell lymphoma cell lines that were sensitive or resistant to TGF-β-induced anti-proliferative effects. Results TGF-β sensitive cell lines expressed higher cell surface levels of the activin receptor-like kinase 5 (Alk-5), a TGF-β receptor type 1. The expression levels of the other TGF-β and bone morphogenetic protein receptors were comparable in the different cell lines. TGF-β-induced phosphorylation of Smad2 was similar in TGF-β sensitive and resistant cell lines. In contrast, activation of Smad1/5 was restricted to cells that were sensitive to growth inhibition by TGF-β. Moreover, with activin A we detected limited anti-proliferative effects, strong phosphorylation of Smad2, but no Smad1/5 phosphorylation. Up-regulation of the TGF-β target genes Id1 and Pai-1 was identified in the TGF-β sensitive cell lines. Constitutive phosphorylation of MAPK p38 was restricted to the TGF-β sensitive cell lines. Inhibition of p38 MAPK led to reduced sensitivity to TGF-β. Conclusions We suggest that phosphorylation of Smad1/5 is important for the anti-proliferative effects of TGF-β in B-cell lymphoma. Alk-5 was highly expressed in the sensitive cell lines, and might be important for signalling through Smad1/5. Our results indicate a role for p38 MAPK in the regulation of TGF-β-induced anti-proliferative effects.

Published
2010
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26. Mass cytometry of follicular lymphoma tumors reveals intrinsic heterogeneity in proteins including HLA-DR and a deficit in non-malignant plasmablast and germinal center B cell populations

Author

Wogsland, Cara Ellen, Greenplate, Allison Rae, Kolstad, Arne, Myklebust, June Helen, Irish, Jonathan Michael, and Huse, Kanutte

Subjects
B-Lymphocytes, Lymphoma, B-Cell, T-Lymphocyte Subsets, Plasma Cells, Humans, HLA-DR Antigens, Flow Cytometry, Germinal Center, Lymphoma, Follicular, Article, Immunophenotyping
Abstract

Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the nonmalignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity.Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, nonmalignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue.Diversity in cellular phenotype between tumors was greater for the malignant B cells than for nonmalignant B or T cells. The malignant B-cell population bore little phenotypic similarity to any healthy B-cell subset, and unexpectedly clustered closer to naïve B-cell populations than GC B-cell populations. Among the nonmalignant B cells within FL tumors, a significant lack of GC and plasmablast B cells was observed relative to tonsil controls. In contrast, nonmalignant T cells in FL tumors were present at levels similar to their cognate tonsillar T-cell subsets.Mass cytometry revealed that diverse HLA-DR expression on FL cells within individual tumors contributed greatly to tumor heterogeneity. Both malignant and nonmalignant B cells in the tumor bore little phenotypic resemblance to healthy GC B cells despite the presence of T follicular helper cells in the tumor. These findings suggest that ongoing signaling interactions between malignant B cells and intra-tumor T cells shape the tumor microenvironment. © 2016 International Clinical Cytometry Society.

Published
2017

27. T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling

Author

Josefsson, Sarah E., primary, Huse, Kanutte, additional, Kolstad, Arne, additional, Beiske, Klaus, additional, Pende, Daniela, additional, Steen, Chloé B., additional, Inderberg, Else Marit, additional, Lingjærde, Ole Christian, additional, Østenstad, Bjørn, additional, Smeland, Erlend B., additional, Levy, Ronald, additional, Irish, Jonathan M., additional, and Myklebust, June H., additional

Published
2018
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41. Bone morphogenetic proteins inhibit CD40L/IL-21-induced Ig production in human B cells: differential effects of BMP-6 and BMP-7.

Author

Huse K, Bakkebø M, Oksvold MP, Forfang L, Hilden VI, Stokke T, Smeland EB, and Myklebust JH

Subjects
CD40 Ligand immunology, Cell Differentiation immunology, Cell Separation, Humans, Immunoglobulin Class Switching immunology, Immunoglobulins immunology, Immunohistochemistry, Interleukins immunology, Plasma Cells cytology, Plasma Cells immunology, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction immunology, Antibody Formation immunology, B-Lymphocytes immunology, Bone Morphogenetic Protein 6 immunology, Bone Morphogenetic Protein 7 immunology, Immunoglobulins biosynthesis, Immunologic Memory immunology, Lymphocyte Activation immunology
Abstract

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily. TGF-β can affect class switch recombination in human B cells, but whether BMPs also play a role have not been tested. We investigated the functional effects of exogenously added BMPs on CD27(-) naive and CD27(+) memory B cells from healthy donors. BMP-2, -4, -6 and -7 inhibited CD40L/IL-21-induced production of IgM, IgG and IgA. BMP-6 reduced Ig production by 70% in memory B cells and more than 55% in naive B cells, whereas the other BMPs were slightly less potent. We observed a striking difference in functional effects between the structurally similar BMP-6 and BMP-7, as BMP-6 mainly inhibited plasmablast differentiation, and BMP-7 mainly induced apoptosis. In memory B cells, BMP-6 upregulated expression of DNA-binding protein inhibitor genes, but potently inhibited CD40L/IL-21-induced upregulation of the transcription factor XBP1, necessary for the late stages of plasmacytic differentiation. Expression of transcription factors regulating earlier stages (IRF4, PRDM1) was not affected by BMP-6. Taken together, these results show that BMPs are potent suppressors of naive and memory B cells., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2011
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